Darkness Before the Dawn - of Biology

By Jack Lucentini

In 1953 a University of Chicago graduate student, Stanley Miller, shot electric sparks
into an apparatus that circulated water, methane, ammonia, and hydrogen in a closed
system. After a week, he identified organic compounds, including amino acids, in the
turbid red liquid that resulted.1 The experiment galvanized research into life's origins.
Yet for decades afterward, the work has proceeded in fits and starts, as scientists
struggled to explain how building-block molecules, scattered throughout a "primordial
soup" of the ancient seas, might have gathered themselves into something resembling
life.

Fifty years later, researchers see new reasons for optimism. In some ways having moved
past building blocks, they have created, under simulated assumed primordial conditions,
larger structures and processes akin to those that characterize cells, including simple
cell membranes, bits of possible early metabolisms, and crude RNA catalysts. Some
investigators even suggest that the creation of artificial cells might be within reach.

LAWYERS AND OCEAN BOTTOMS - Several factors have driven this work, "reenergizing
a field that's been around for a long time," says George Cody, a senior research
scientist at the Carnegie Institution of Washington, DC. A major factor, he
says, was the 1979 discovery of microbes thriving on chemicals released at deep-sea
hot springs, or hydrothermal vents. The findings prompted speculation that life
originated in similar habitats. A German patent lawyer and biochemist, Günter
Wächtershäuser, later developed a detailed theory of how the earliest metabolic
cycles could have functioned there. This proposal, in turn, inspired streams
of useful experiments, Cody says, despite being controversial. Some, including
Cody, don't fully buy it.

Michael J. Russell, a research professor at the Scottish Universities Research and
Reactor Centre, credits advances in biochemistry and geochemistry with fueling
origins-of-life research. The two approaches seem to be converging, he wrote in a recent
commentary, such that "the experimental quest for the recipe for 'protolife' can begin
in earnest."2

A possible bit of this recipe accompanied the commentary. Martin M. Hanczyc and
colleagues at Massachusetts General Hospital in Boston reported that clay particles
catalyzed the conversion of molecular precursors into bilayer membrane sacs containing
RNA. Forcing these sacs through narrow pores made them divide, allowing cycles of
division and regrowth.3 The artificiality of this extrusion procedure, the authors
concede, probably means it has no natural analogue. Russell, more optimistically,
suggests that porous clays near relatively cool hydrothermal vents might permit such
processes. The "first cells would have had to divide or bud and, at the same time, pass
on a code for growth and maintenance," he wrote.

The findings also show how "the mineral-water interface is likely to have been important
in organizing some of the compounds" of early life, notes David Deamer, a professor of
chemistry and biochemistry at the University of California, Santa Cruz. This observation
echoes other research, based on Wächtershaüser's theory, which suggests early metabolic
cycles also might have occurred at such interfaces. Wächtershaüser developed the proposal
by calculating backward from modern organisms' metabolic cycles, to derive a putative
original cycle. This cycle predated cells, he contends, taking place first at mineral
surfaces, which served both as catalysts and as stages to bring the reactants together.
Only later did membranes encapsulate the reacting chemicals and drift off these surfaces
for an independent life.

Wächtershaüser claims the key primordial metabolic cycle resembled the reductive
citric acid cycle, which operates in vent-dwelling archaebacteria. It is essentially
the reverse of the citric acid cycle, which generates energy and expels carbon
dioxide. Wächtershäuser's proposed cycle takes up carbon monoxide as a carbon
source for the organism, and runs on energy from oxidation of vent minerals.

Other researchers, including Claudia Huber of Munich Technical University,
who works with Wächtershäuser, and Cody, who works separately, have conducted
experiments that they say support key parts of the theory. They have played
out parts of the cycle under conditions designed to mimic those near vents,
albeit with more concentrated reactants.4 Under similar conditions, they have
demonstrated amino acid synthesis, and peptide assembly and disassembly, all
crucial metabolic processes.5 In a surprise side reaction, Wächtershäuser says,
this disassembly also produced a precursor to purines, components of nucleic
acids, suggesting these might have co-evolved with peptides. "It's exciting
the way you can open a door, come into a room and find a hundred doors," Wächtershäuser
remarks.

NEW RECIPE, NEW SOUP - The vent hypothesis has stolen some attention from the prevailing
"primordial soup" model of life's origins, which burst onto the stage with Miller's
experiment. It held that life originated in the oceans by feeding on small, organic
molecules and getting energized by a highly reducing atmosphere and energy sources such
as sunlight or lightning. Vent theories gained currency after it emerged that conditions
nearer the ocean surface could have been hostile to life. The atmosphere might have been
less reducing than once supposed, and constant meteor and comet bombardments could have
shattered each fragile new beginning. The vents might have provided a safer environment.

But debate abounds. The vent hypothesis itself is actually several hypotheses.
Wächtershaüser claims that the first organisms were autotrophs, feeding off chemical
energy from inorganic chemicals spewing from vents. This separates him from virtually
all other researchers, who contend that early organisms were heterotrophic, nourishing
themselves on small organic molecules. "If we've been more and more successful at
showing how the natural world comes up with these interesting [organic] substrates, why
would the first organism completely ignore that?" Cody remarks.

Other researchers stick to the soup recipe. Wächtershaüser's model is "not relevant to
the question of the origin of life as we know it," writes Jeffrey L. Bada, director of
the NASA Specialized Center of Research and Training in Exobiology at the Scripps
Institution of Oceanography in La Jolla, Calif., in an E-mail. Bada has argued that the
vents' high temperatures would destabilize organic compounds. He also disputes findings,
sometimes cited in support of the vent scenario, that heat-loving organisms occupy the
evolutionary tree's deepest branches.6

Bada, Miller, and others advocate an updated version of the soup theory. Miller recently
proposed that although a strongly reducing primordial atmosphere, crucial to the original
theory, is now in doubt, a more weakly reducing one would suffice. His team irradiated a
weakly reducing mixture of putative, primordial atmospheric gases with protons and
obtained, they wrote, bioorganic compounds in amounts comparable to those that a strongly
reducing atmosphere would yield.7 Bada also has explored the possibilities that
meteorites might have deposited organic compounds on Earth, and that repeated freeze-thaw
cycles on the planet might have stimulated organic compound synthesis.

ULTIMATE PROOF OF LIFE - The debate is "tending to fuel good science," says Matthew Levy,
a postdoctoral researcher at the University of Texas at Austin. He participates in yet
another line of research, the evolution of RNA. Driving this work is a belief that RNA
might have been the first self-replicating system, because its ability to act as both
enzyme and coding template would resolve a conundrum over which one came first.
Researchers have made some progress in artificially "evolving" short oligonucleotides
that can catalyze their own replication and perhaps such biologically relevant functions
as redox chemistry.8

Other factors boosting origins-of-life research include improved technology, which lets
researchers better assess synthesized organic molecules. Such methods have come a long
way since the paper chromatography of Miller's 1953 experiment.1 "The technology has
made performing tasks of chemistry, which used to be daunting, routine," says Jason
Dworkin, an astrobiologist at NASA's Goddard Space Flight Center, Greenbelt, Md.

Other recent advances, some scientists suggest, may put the ultimate origins-of-life
experiment within reach: the creation of an artificial cell. Deamer has taken steps in
this direction. He and colleague Pierre-Alain Monnard enclosed a strip of template DNA
and polymerase in a bilayer lipid membrane; they reported that the sac drew in
ribonucleotides surrounding it to synthesize RNA.9 A replicating, evolving system could
be a next step, Deamer and colleagues contend: "The goal of future investigations will
be to fabricate artificial cells as models of the origin of life."